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Mechanisms and impact of the frequent exacerbator phenotype in chronic obstructive pulmonary disease.

Wedzicha JA, Brill SE, Allinson JP, Donaldson GC - BMC Med (2013)

Bottom Line: This is relatively stable over time, occurs across disease severity, and is associated with poorer health outcomes.Overall these patients have poorer health status, accelerated forced expiratory volume over 1 s (FEV1) decline, worsened quality of life, and increased hospital admissions and mortality, contributing to increased exacerbation susceptibility and perpetuation of the frequent exacerbator phenotype.This review article sets out the definition and importance of the frequent exacerbator phenotype, with a detailed examination of its pathophysiology, impact and interaction with other comorbidities.

View Article: PubMed Central - HTML - PubMed

Affiliation: Centre for Respiratory Medicine, Royal Free Campus, University College London, Rowland Hill Street, Hampstead, London NW3 2PF, UK. w.wedzicha@ucl.ac.uk

ABSTRACT
Exacerbations of chronic obstructive pulmonary disease (COPD) are important events that carry significant consequences for patients. Some patients experience frequent exacerbations, and are now recognized as a distinct clinical subgroup, the 'frequent exacerbator' phenotype. This is relatively stable over time, occurs across disease severity, and is associated with poorer health outcomes. These patients are therefore a priority for research and treatment. The pathophysiology underlying the frequent exacerbator phenotype is complex, with increased airway and systemic inflammation, dynamic lung hyperinflation, changes in lower airway bacterial colonization and a possible increased susceptibility to viral infection. Frequent exacerbators are also at increased risk from comorbid extrapulmonary diseases including cardiovascular disease, gastroesophageal reflux, depression, osteoporosis and cognitive impairment. Overall these patients have poorer health status, accelerated forced expiratory volume over 1 s (FEV1) decline, worsened quality of life, and increased hospital admissions and mortality, contributing to increased exacerbation susceptibility and perpetuation of the frequent exacerbator phenotype. This review article sets out the definition and importance of the frequent exacerbator phenotype, with a detailed examination of its pathophysiology, impact and interaction with other comorbidities.

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Association of disease severity with the frequency and severity of exacerbations. Reproduced from Hurst et al. [3] with permission.
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Figure 1: Association of disease severity with the frequency and severity of exacerbations. Reproduced from Hurst et al. [3] with permission.

Mentions: It has also been recognized that some patients with COPD are particularly susceptible to exacerbations and these patients have been termed ‘frequent exacerbators’, in contrast to patients with infrequent exacerbations who experience few exacerbations over time. The frequent exacerbator phenotype has now been recognized as a major phenotype in patients with COPD and occurs across disease severities. The Evaluation of COPD Longitudinally to Identify Predictive Surrogate Endpoints (ECLIPSE) exacerbation study showed that even in patients defined as grade 2 according to the Global Initiative for Chronic Obstructive Pulmonary Disease (GOLD) (forced expiratory volume over 1 s (FEV1) 50% to 80% predicted), 22% of the COPD population were frequent exacerbators [3] (Figure 1). Therefore, this review will describe the pathophysiology and impact of the frequent exacerbator phenotype and will also address the interaction with comorbidity, as illustrated in Figure 2.


Mechanisms and impact of the frequent exacerbator phenotype in chronic obstructive pulmonary disease.

Wedzicha JA, Brill SE, Allinson JP, Donaldson GC - BMC Med (2013)

Association of disease severity with the frequency and severity of exacerbations. Reproduced from Hurst et al. [3] with permission.
© Copyright Policy - open-access
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3750926&req=5

Figure 1: Association of disease severity with the frequency and severity of exacerbations. Reproduced from Hurst et al. [3] with permission.
Mentions: It has also been recognized that some patients with COPD are particularly susceptible to exacerbations and these patients have been termed ‘frequent exacerbators’, in contrast to patients with infrequent exacerbations who experience few exacerbations over time. The frequent exacerbator phenotype has now been recognized as a major phenotype in patients with COPD and occurs across disease severities. The Evaluation of COPD Longitudinally to Identify Predictive Surrogate Endpoints (ECLIPSE) exacerbation study showed that even in patients defined as grade 2 according to the Global Initiative for Chronic Obstructive Pulmonary Disease (GOLD) (forced expiratory volume over 1 s (FEV1) 50% to 80% predicted), 22% of the COPD population were frequent exacerbators [3] (Figure 1). Therefore, this review will describe the pathophysiology and impact of the frequent exacerbator phenotype and will also address the interaction with comorbidity, as illustrated in Figure 2.

Bottom Line: This is relatively stable over time, occurs across disease severity, and is associated with poorer health outcomes.Overall these patients have poorer health status, accelerated forced expiratory volume over 1 s (FEV1) decline, worsened quality of life, and increased hospital admissions and mortality, contributing to increased exacerbation susceptibility and perpetuation of the frequent exacerbator phenotype.This review article sets out the definition and importance of the frequent exacerbator phenotype, with a detailed examination of its pathophysiology, impact and interaction with other comorbidities.

View Article: PubMed Central - HTML - PubMed

Affiliation: Centre for Respiratory Medicine, Royal Free Campus, University College London, Rowland Hill Street, Hampstead, London NW3 2PF, UK. w.wedzicha@ucl.ac.uk

ABSTRACT
Exacerbations of chronic obstructive pulmonary disease (COPD) are important events that carry significant consequences for patients. Some patients experience frequent exacerbations, and are now recognized as a distinct clinical subgroup, the 'frequent exacerbator' phenotype. This is relatively stable over time, occurs across disease severity, and is associated with poorer health outcomes. These patients are therefore a priority for research and treatment. The pathophysiology underlying the frequent exacerbator phenotype is complex, with increased airway and systemic inflammation, dynamic lung hyperinflation, changes in lower airway bacterial colonization and a possible increased susceptibility to viral infection. Frequent exacerbators are also at increased risk from comorbid extrapulmonary diseases including cardiovascular disease, gastroesophageal reflux, depression, osteoporosis and cognitive impairment. Overall these patients have poorer health status, accelerated forced expiratory volume over 1 s (FEV1) decline, worsened quality of life, and increased hospital admissions and mortality, contributing to increased exacerbation susceptibility and perpetuation of the frequent exacerbator phenotype. This review article sets out the definition and importance of the frequent exacerbator phenotype, with a detailed examination of its pathophysiology, impact and interaction with other comorbidities.

Show MeSH
Related in: MedlinePlus